Coffee is emerging as a protective agent against a number of diseases,...

Coffee is emerging as a protective agent against a number of diseases, including cancer. A study published last week in Cancer, Epidemiology, Biomarkers, and Prevention shows that women who drank more than four cups of coffee per day cut their risk of endometrial cancer by 25% compared with those who drank less than one cup per day.[1]

Although the mechanism for the reduced risk is not clear, the authors postulate that the antioxidant properties of coffee, rather than caffeine are responsible for the benefit. Senior author of the study, Edward Giovannucci, MD, ScD, professor of nutrition and epidemiology at the Harvard School of Public Health, says the benefit appears to be linked to obesity, estrogen, and insulin.

“Coffee has already been shown to be protective against diabetes due to its effect on insulin,” said Giovannucci. “So we hypothesized that we’d see a reduction in some cancers as well.”

Because coffee consumption is so widespread, the authors suggest that it may be a strategy, in addition to maintaining normal body weight and exercising, to reduce the risk of endometrial cancer, but they stress that the benefit was seen with black coffee and warn that adding sugar and cream to your coffee may offset the benefits found in the study.

A previously published, prospective, long-term study by Woroger et al, which was similar in methodology to the current study, had shown a modest inverse association between caffeine consumption and ovarian cancer risk, which was strongest among women who had never used either oral contraceptives or postmenopausal hormones.[2]

“High levels of estrogen and insulin are strong risk factors for endometrial cancer risk, and increasing epidemiologic evidences show an inverse association between coffee intake and those hormone levels, and thus we hypothesized that high coffee intake may reduce the risk of endometrial cancer through the hormonal modulation of coffee intake,” explained Youjin Je, a doctoral candidate, and first author of the study. “Based on our results and those from the recent large prospective study (NIH-AARP Diet and Health Study, IJC), it suggests that compounds, other than, or in addition to, caffeine, may contribute to the inverse association of coffee intake with endometrial cancer risk.”

The Rationale and Study Design

Coffee consumption may be related to endometrial cancer risk as endometrial cancer is associated with exposure to higher levels of estrogen and insulin and the caffeine and its components in coffee may be related to lower levels of these hormones. Studies have shown that coffee and caffeine influenced circulation levels of sex hormone binding globulin and free estradiol and retrospective studies reported an inverse association between coffee consumption and endometrial cancer risk.

The current study is the first long-term follow up prospective study to examine the relationship of caffeine and endometrial cancer and whether intake of decaffeinated coffee or tea has an effect on cancer risk given the limited prospective data on this topic.

The cohort of subjects was 67,470 female nurses from 11 states between the age of 34 and 59. Their baseline caffeine consumption was evaluated and the women were followed starting in 1980. The women answered questionnaires about lifestyle, food, and alcohol consumption.

The Results

Women on the study were followed up for 26 years and 672 cases of endometrial cancer were documented. Women who drank four cups of coffee per day had a 25% lower risk of of endometrial cancer than those who consumed less than one cup per day (P = .02). Those women that drank two to three cups a day had a 7% reduced risk. A similar association was found with caffeinated coffee consumption. Women who drank decaffeinated coffee had a 22% reduced risk of endometrial cancer. However, the study was likely underpowered to detect a significant association with decaffeinated coffee intake because less than 2% of the study population consumed four or more cups of decaffeinated coffee per day.

Further analysis showed a stronger inverse association of high coffee intake among three subgroups. Obese women who drank high amounts of coffee daily had a lower cancer risk. The authors attribute this result in obese women with insulin resistance and oxidative stress as the potential ability of coffee to improve these conditions. Additionally, there was also a stronger inverse association of high coffee intake and women who have ever smoked. An inverse relationship was seen for postmenopausal women but not premenopausal women. The authors believe that the hormonal modulation of coffee on the endometrium is more notable for women who have naturally lower estrogen levels such as postmenopausal women.

Because the study was self-reporting, there is potential for measurement errors of dietary assessment, caffeine consumption and the variability of cup size and strength of the coffee between individuals in the study. While the authors controlled for potential confounding factors, residual confounding factors and unmeasured habits associated with coffee drinking such as the addition of cream and sugar to the daily coffee may need further follow-up. Giovannucci said that he hopes the study will lead to further investigations and randomized studies about the effect of coffee and its components on cancer.

According to Je, there have been three large prospective studies conducted in Sweden[3] and the United States[4]; Nurses' Health Study[1]) that “have suggested strong benefits of coffee drinking, especially among overweight or obese women, which is consistent with the notion that insulin resistance and hyperinsulinemia may be involved in the process.” However, she adds, “to make specific recommendations of coffee intake in reducing the risk of endometrial cancer, more large studies are needed to determine subgroups to obtain more benefits from coffee drinking in relation to endometrial cancer risk.”

As far as a mechanism for the inverse relationship between coffee intake and endometrial cancer risk, Je points to several of the components in coffee that have antioxidant properties. “Chlorogenic acid and caffeic acid in coffee have strong antioxidant properties that can prevent oxidative DNA damage, and improve insulin sensitivity,” Je said. “In addition, caffeine and other bioactive compounds in coffee seem to increase the clearance of estrogen.”

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